Significance Animal models of human genetic diseases are essential for developing therapies.Models can be created in mice, but the many differences between mice and humans often renders such models less informative. Primate models are especially important for diseases that affect the organism's immune system or behavior, as well as diseases for which mouse models have proven to be inadequate. Objectives To discover natural animal models of human recessive genetic diseases. In this study, cystic fibrosis is used as the model genetic disease. Genomic DNA was purified from 1300 primates (~400 from CRPRC) and scanned for mutations using SSCP. The project is feasible even for rare recessive diseases, because a disease frequency of 1 per million has a carrier frequency of 1/500. Results Forty coding changes have been identified; 20 alter amino acids that are absolutely conserved across all species tested to date. By inspection, none of these would obviously inactivate the protein, so functional testing is required. At least 3 of the candidate mutations impair function. Future Directions We will test additional primates, refine the physiological assays, and begin breeding carriers of candidate recessive mutations. KEYWORDS cystic fibrosis, genetic disease